Modelling Virus and Antibody Dynamics during Dengue Virus Infection Suggests a Role for Antibody in Virus Clearance

Hannah E Clapham, Than Ha Quyen, Duong Thi Hue Kien, Ilaria Dorigatti, Cameron P Simmons and Neil M Ferguson

PLOS Computational Biology, 2016, vol. 12, issue 5, 1-15

Abstract: Dengue is an infection of increasing global importance, yet uncertainty remains regarding critical aspects of its virology, immunology and epidemiology. One unanswered question is how infection is controlled and cleared during a dengue infection. Antibody is thought to play a role, but little past work has examined the kinetics of both virus and antibody during natural infections. We present data on multiple virus and antibody titres measurements recorded sequentially during infection from 53 Vietnamese dengue patients. We fit mechanistic mathematical models of the dynamics of viral replication and the host immune response to these data. These models fit the data well. The model with antibody removing virus fits the data best, but with a role suggested for ADCC or other infected cell clearance mechanisms. Our analysis therefore shows that the observed viral and antibody kinetics are consistent with antibody playing a key role in controlling viral replication. This work gives quantitative insight into the relationship between antibody levels and the efficiency of viral clearance. It will inform the future development of mechanistic models of how vaccines and antivirals might modify the course of natural dengue infection.Author Summary: Dengue is a globally important viral disease. Despite this, there is still much unknown about the immunology, virology and epidemiology of dengue. As for all viral infections, the interaction between virus and immune response is a complex one. Using data collected from patients, we model how the virus replicates in an infected individual and how the human antibody response acts to control that replication. We show that the timing and magnitude of the growth and decline of virus and antibody levels in dengue-infected patients are consistent with antibody playing a key role in controlling infection. Our results are of use in the evaluation of potential antiviral drugs and vaccines.

Date: 2016
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Persistent link: https://EconPapers.repec.org/RePEc:plo:pcbi00:1004951

DOI: 10.1371/journal.pcbi.1004951

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